Dendritic Cells (DC) are key antigen presenting cells in the immune response, and DC-SIGN is an antigen capture receptor expressed by DC. The DC-SIGN mediated process of antigen capture and internalization is exploited by HIV-1 as a means of viral dissemination to T cells, and DC-SIGN is necessary for DC-mediated infection of T cells "in trans". Interestingly, membrane DC-SIGN forms 100-200 nm clusters in a ligation- independent manner, and these structures are thought to represent high avidity binding sites necessary for efficient binding of -120 nm diameter HIV-1 virions. However, the clustering of DC-SIGN on live cells and its membrane dynamics require further characterization. Due to the importance of DC-SIGN for HIV-1 trans- infection of T cells and the potential role of these organized membrane structures as ports for viral binding and entry into DC, it will be important to investigate the membrane distribution and mobility of DC-SIGN clusters and individual proteins in live DC. The proposed work focuses on 1) biophysical characterization of membrane DC-SIGN with respect to clustering and cluster mobility on the plasma membrane and 2) underlying molecular mechanisms that may account for the membrane distribution of DC-SIGN. [unreadable] [unreadable] [unreadable]